With the renewed interest in the use of ENU mutagenesis has come the recognition that this technique creates an unexpected (if not undesirable) problem; namely, how to efficiently maintain a large number of mutants and prioritize these for further investigation. The determination of the genetic map position of a mutant, even at low resolution, can effectively serve these ends. Map position can be very important for assessing whether a mutant represents a re-mutation of a known gene or a mutation at a novel locus. Map location can also suggest candidate loci for examination by sequence or expression analysis. Additionally, the definition of a recombinant interval carrying a mutation allows one to identify heterozygous carriers by genotype analysis, rather than the more tedious, expensive, and time-consuming strategy of progeny testing. In this project, we propose to generate and import mice carrying mutations affecting development, and map these loci using a haplotype analysis approach that requires small numbers of affected animals. Mice that appear to be re-mutations at known loci (based on phenotype and map position) will then be excluded, and mice with presumptive novel mutations will be further analyzed at various embryonic stages by histological analysis and using in situ or immunohistochemical analysis. All of these results will be posted and mice will be available to any interested investigator. Finally, for a small number of mice, we will attempt to identify the causal locus by positional cloning, with an aim towards developing the most efficient protocols for this.